Metformin Attenuates Partial Epithelial-Mesenchymal Transition in Salivary Gland Inflammation via PI3K/Akt/GSK3ß/Snail Signaling Axis.

Chronic inflammation in the salivary glands (SG) often triggers epithelial-mesenchymal transition (EMT), leading to the loss of acinar function and promoting fibrosis. This study explores the role of Metformin in mitigating partial EMT in SG inflammation. In vitro, human salivary gland epithelial cells (hSGECs) were treated with lipopolysaccharide (LPS) and Metformin. EMT markers and the PI3K/Akt/GSK3ß/Snail signaling axis were assessed using RNA-seq and Western blot analysis. In vivo, a Wharton's duct ligation rat model was employed to mimic chronic sialadenitis (CS). Nine Wistar rats were randomly divided into three groups: Control, Ligation and Ligation + Metformin groups, with three rats per group. After ductal ligation, the Ligation + Metformin group received 100 mg/kg of Metformin via intragastric administration, while the Control and Ligation groups received an equivalent saline every 24 h. Histological analysis, immunohistochemical and immunofluorescence staining were conducted to evaluate acinar morphology, EMT, and the PI3K/Akt/GSK3ß/Snail signaling axis. The results showed that in CS tissues, atrophied acinar cells underwent partial EMT. In vitro, Metformin reversed LPS-induced EMT in hSGECs. RNA-seq and Western blot revealed that Metformin achieved this effect by targeting the PI3K/Akt/GSK3ß/Snail signaling axis (P < 0.01). In ductal ligation models, Metformin treatment restored ligation-induced acinar damage and functional loss (P < 0.01). Further histological evidence supported that Metformin mitigated EMT by inhibiting inflammatory activation of PI3K/Akt/GSK3ß/Snail signaling axis (P < 0.01). In conclusion, Metformin alleviates partial EMT in SG inflammation by targeting the PI3K/Akt/GSK3ß/Snail signaling axis, highlighting its potential as a therapeutic strategy for SG inflammation.

Driving low-carbon mechanisms through smart investments in renewable resources and green finance initiatives among G20 nations.

In light of the escalating concerns regarding climate change and environmental decline, major nations are actively exploring strategies to mitigate environmental harm and achieve future sustainability. The surge in economic expansion in developed economies is linked to an increase in CO2 emissions. Consequently, in their pursuit of carbon-neutral policies, these countries are increasingly turning towards renewable energy as a means to enhance resource conservation and efficiency. This research investigates the varied impacts of renewable energy investment, green finance, geopolitical risk, GDP growth, foreign direct investment, and gross fixed capital formation on the carbon emissions of G20 countries. The study uses the CUP-FM (Continuously Updated Fully Modified) and CUP-BC (Continuously Updated Bias-Corrected) estimators, which are sophisticated econometric approaches designed to handle non-stationary panel data and cross-sectional dependency, to produce robust long-term parameter estimates. The CUP-FM estimator adjusts for potential endogeneity and serial correlation, improving the accuracy of long-run relationships in panel data. The CUP-BC estimator provides bias-corrected estimates to further enhance the precision of these long-run connections.The long-term parameter estimates reveal a negative correlation between renewable energy investment, green finance, and carbon emissions. In contrast, foreign direct investment, gross fixed capital formation, GDP growth, and geopolitical risk are positively associated with CO2 emissions. This suggests that financial stability often leads to investments in carbon-heavy economic ventures, thereby implicating economic growth as a contributing factor to environmental degradation in G20 countries.

Integrating Contrastive Learning and Cycle Generative Adversarial Networks for Non-invasive Fetal ECG Extraction.

Fetal electrocardiogram (FECG) contains crucial information about the fetus during pregnancy, making the extraction of FECG signal essential for monitoring fetal health. However, extracting FECG signal from abdominal electrocardiogram (AECG) poses several challenges: (1) FECG signal is often contaminated by noise, and (2) FECG signal is frequently overshadowed by high-amplitude maternal electrocardiogram (MECG). To address these issues and enhance the accuracy of signal extraction, this paper proposes an improved Cycle Generative Adversarial Networks (CycleGAN) with integrated contrastive learning for FECG signal extraction. The model introduces a dual-attention mechanism in the generator of the generative adversarial network, incorporating a multi-head self-attention (MSA) module and a channel-wise self-attention (CSA) module to enhance the quality of generated signals. Additionally, a contrastive triplet loss is integrated into the CycleGAN loss function, optimizing training to increase the similarity between the extracted FECG signal and the scalp fetal electrocardiogram. The proposed method is evaluated using the ADFECG dataset and the PCDB dataset both from the Physionet. In terms of signal extraction quality, Mean Squared Error is reduced to 0.036, Mean Absolute Error (MAE) to 0.009, and Pearson Correlation Coefficient reaches 0.924. When validating the model performance, Structural Similarity Index achieves 95.54%, Peak Signal-to-Noise Ratio (PSNR) reaches 38.87 dB, and R-squared (R2) attains 95.12%. Furthermore, the positive predictive value (PPV), sensitivity (SEN) and F1-score for QRS wave cluster detection on the ADFECG dataset also reached 99.56%, 99.43% and 99.50%, respectively. On the PCDB dataset, the positive predictive value (PPV), sensitivity (SEN) and F1-score for QRS wave cluster detection also reached 98.24%, 98.60% and 98.42%, respectively. All of them are higher than other methods. Therefore, the proposed model has important applications in effective monitoring of fetal health during pregnancy.

Hypoglycemic effect of orally administered resistant dextrins prepared with different acids on type 2 diabetes mice induced by high-fat diet and streptozotocin.

A comparative study was performed to investigate the physicochemical properties and protective effects of hydrochloric acid-resistant dextrin (H-RD), citric acid-resistant dextrin (C-RD) and tartaric acid-resistant dextrin (T-RD) on the metabolic disorders and intestinal microbiota for type 2 diabetes mellitus (T2DM) mice. T-RD had the minimum molecular weight, with the highest short chain (DP 6-12) proportion and resistant starch content. After 4-week intervention with the three resistant dextrins, the body weight and fasting blood glucose of T2DM mice were improved significantly, accompanied by the reduction of serum indexes (TG, TC, LDL-C, ALT, AST, CRE, BUN, FINS, and GSP), but the serum HDL-C and liver glycogen levels increased. Among the three RDs intervention groups, T-RD showed the most significant improvement, followed by C-RD and finally H-RD. The 16 s rDNA results indicated that oral administration of resistant dextrins favored the proliferation of specific gut microbiota, including Faecalibaculum, Parabacteroides and Dubosiella, and reduced the ratio of Firmicutes/Bacteroidota, which is beneficial for reducing insulin resistance. Herein, the findings supported that the resistant dextrins exhibited a remission effect on T2DM, providing a basis for the development of functional food adjuvants for T2DM treatment.

Binocular Visual Deficits at Low to High Spatial Frequency in Intermittent Exotropia After Surgery.

Purpose: To investigate binocular visual deficits at low to high spatial frequencies in patients with intermittent exotropia (IXT) after surgical correction, using the binocular orientation combination task. Methods: Thirteen patients whose IXT has been aligned surgically (17 ± 4.8 years old; 7 females) and 13 normal individuals (21.8 ± 2.5 years old; 6 females) were recruited. All participants had normal or corrected-to-normal visual acuity. The IXT patients had undergone surgery at least one month prior to the study and achieved successful eye alignment post-surgery. We measured participants' balance points (BPs), defined as the interocular contrast ratio (nondominant eye/dominant eye) when both eyes contributed equally to binocular combination, using the binocular orientation combination task at three spatial frequencies (0.5, 4.0, and 8.0 cycles/degree). The absolute values of log10(BP) (i.e., |logBP|) and the area under of the |logBP| versus spatial frequency curve were used to quantify the extent of binocular imbalance. Results: Surgery aligned the eye position of patients with IXT, with a postoperative exodeviation of -4.92 ± 4.29 prism diopters at distance. Participants' |logBP| values showed significant differences between groups, F(1,24) = 9.175, P = 0.006, and across spatial frequencies, F(2,48) = 7.127, P = 0.002. However, the interaction between group and spatial frequency was not significant, F(2,48) = 0.379, P = 0.687. Conclusions: Patients whose IXT has been alighted surgically experience binocular imbalance across a wide range of spatial frequencies, with greater binocular imbalance occurring at high spatial frequencies than low spatial frequencies.

Carthamin yellow alleviates dextran sodium sulfate-induced ulcerative colitis by repairing the intestinal barrier and activating the Nrf2/GPX4 axis.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD). There is a growing prevalence of UC, but current conventional drugs lack efficacy. Carthamin yellow (CY) is a flavonoid compound extracted from safflower that is widely used and has various pharmacological effects. In the present study, we established colitis models in mice via DSS and in Caco-2 cells via lipopolysaccharide (LPS). Our results showed that CY treatment attenuated the symptoms of colitis by decreasing colonic pathological damage and improving disease activity index (DAI) scores. Notably, we observed that CY treatment decreased the levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1ß) by inhibiting the NLRP3/Caspase-1/IL-1ß and MAPK/NF-κB signaling pathways. Moreover, we verified that treatment with CY obviously improved intestinal barrier function in both DSS-induced mice and LPS-stimulated Caco-2 cells. Ferroptosis-related markers were assessed. CY attenuated DSS-induced colitis by inhibiting ferroptosis, as assessed by Fe2+ accumulation, total antioxidant capacity (T-AOC), and reactive oxygen species (ROS), 4-hydroxynonenal (4-HNE), and glutathione (GSH) levels. Additionally, there was an increase in superoxide dismutase (SOD) and catalase (CAT) activity, as well as alterations in ferroptosis-related protein and gene expression (ACSL4, GPX4, SLC7A11, TfR1, and FTH1). Further analyses revealed that CY could inhibit ferroptosis via the Nrf2/GPX4 axis in both in vivo and RSL3-induced Caco-2 cell models. Importantly, the antiferroptotic and protective effects of CY were nullified by Nrf2 knockout in vivo and by the use of ML385 in vitro. In conclusion, the effects of CY on UC are strongly associated with the Nrf2 pathway. CY might be a potential candidate for the treatment of UC. Therefore, our results provide an important reference for investigating the mechanisms of flavonoid compounds involved in preventing inflammatory diseases.

Effect of an evidence-based early rehabilitation program on adult patients with venovenous extracorporeal membrane oxygenation: A cohort study.

OBJECTIVES: To assess the efficacy of early rehabilitation program for VV-ECMO patients and observe the influence on the respiratory and skeletal muscles. DESIGN: A cohort study. SETTING: The study was conducted with VVECMO patients in a comprehensive ICU with 32 beds. MAIN OUTCOME MEASURES: Ultrasound measurements were performed on each patients on day 1, 4, 7, 10, and 14, including diaphragmatic excursion (DE), diaphragmatic thickening fraction (DTF), intercostal muscle thickening fraction (ICMTF), thickness of the rectus femoris (RF), thickness of vastus intermedius (VI), and rectus femoris cross-sectional area (RF-CSA). Data on basic characteristics, results of ultrasound measurements, patients outcomes and adverse events were collected. RESULTS: 22 patients received usual rehabilitation measures were set as the control group and 23 patients underwent early rehabilitation program were set as the study group. There were no differences in diaphragmatic excursion, diaphragmatic thickening fraction, intercostal muscle thickening fraction, thickness of rectus femoris, thickness of vastus intermedius, rectus femoris cross-sectional area between two groups on day 1 after VV-ECMO treatment (P > 0.05). The variation of diaphragmatic thickening fraction and intercostal muscle thickening fraction decreased on the day 7 and 14 after treatment (P < 0.05). The variation of vastus intermedius thickness and rectus femoris cross-sectional area in the study group was less compared with those in the control group on day 4, 7, 10 and 14. The ECMO duration in the study group was shorter than that in the control group (12.00 [10.00-16.25] days vs. 8.00 [6.00-12.25] days, P = 0.002), but there was no difference in the duration of mechanical ventilation. CONCLUSION: Early rehabilitation program can ameliorate muscle atrophy. We recommend implementation of our rehabilitation program in VV-ECMO patients. This program can improve skeletal muscle atrophy and dysfunction in patients with VV-ECMO effectively and perhaps improve quality of life for patients in the future. IMPLICATIONS FOR CLINICAL PRACTICE: Early rehabilitation program put higher demands bedside nurses. It requires them to observe conditions of VVECMO patients closely, assess the feasibility of rehabilitation promptly, and monitor for any adverse reactions. Ultrasound measurement is a noninvasive and useful tool to assess muscle atrophy in ICU patients. Early rehabilitation program can improve skeletal muscle atrophy and dysfunction in patients with VV-ECMO effectively.

The Value of CEUS LI-RADS combined with AFP in early diagnosis of hepatocellular carcinoma in low- and high-risk patients.

BACKGROUND: We found that the occurrence of hepatocellular carcinoma (HCC) has increased significantly in non-cirrhotic individuals, with HCC being frequently overlooked or misdiagnosed. Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is known to have a high diagnostic quality in high-risk HCC patients. Therefore, we aimed to compare the detection accuracy of CEUS LI-RADS for HCC between low- and high-risk individuals, to confirm its value in low-risk patients at increased risk of HCC, but not yet included in the high-risk groups of LI-RADS. In addition, since CEUS LR-4 and LR-M categories contain a relatively high proportion of HCC, and serum alpha-fetoprotein (AFP) is the most commonly used biomarker for HCC, and the clinically valid, we attempted to further improve the early diagnostic capability of CEUS LI-RADS for HCC in the low-risk and high-risk patients by combining CEUS LR-4 and LR-M categories with AFP. METHODS: We defined high-risk groups (HR)-included in the high-risk patients of LI-RADS, low-risk groups (LR)-not included in the high-risk patients of LI-RADS and enrolled 189 HCC patients with LR and HR settings in a retrospective study. All lesions were confirmed histopathologically. The CEUS LI-RADS accuracy for detecting HCC in these two patients was compared. In addition, the diagnostic algorithm in our study was proposed (for CEUS LR-4 and LR-M patients with AFP>20 ng/ml). we analyzed the ability of CEUS LI-RADS as a valid method of establishing the early diagnosis of HCC in LR and HR patients by combining LR-4 and LR-M categories with AFP. RESULTS: Through comparative analysis, the specificity of the CEUS LR-5 category for HCC in the HR group was 78.4%, whereas in the LR group, it was 94.2%. Meanwhile, the sensitivity (63.2% vs. 63.0%) and positive predictive value (PPV) (75.0% vs. 88.7%) did not differ between the LR and HR groups ( P = 0.990, P = 0.299). It is noteworthy that there were the high proportion of HCC in CEUS LR-4 and LR-M categories in our cases and when we combined CEUS LR-4 and LR-M categories with AFP significantly improved the sensitivity by 21.0% (84.2%) in the LR group, and by 16.0% (79.0%) in the HR group, with statistically difference in sensitivity after combination in the HR group ( P = 0.014). CONCLUSIONS: The CEUS LR-5 category has real meaningful utility in the diagnosis of HCC in both LR and HR patients. The early detection power of the CEUS LI-RADS category for HCC patients was further increased when the CEUS LR-4 and LR-M categories were combined with elevated AFP.

Frailty and socioeconomic position: A systematic review of observational studies.

BACKGROUND: Frailty, an age-related state of reduced physiological reserve, is often associated with lower socio-economic position (SEP). This systematic review synthesised observational studies assessing (i) the association between SEP and frailty prevalence; (ii) how changes in frailty status over time vary by SEP; and (iii) whether the association between frailty and clinical outcomes is modified by SEP. METHODS: We searched three electronic databases from 2001 to 2023. We included observational studies measuring early-, mid-, and late-life indicators of SEP (education, income, wealth, housing, occupation, and area-based measures of multiple deprivation) and frailty (assessed using any validated measure). Screening and extraction were performed in duplicate. Findings were synthesised using narrative synthesis. RESULTS: We included 383 studies reporting findings from 265 independent samples/cohorts across 64 countries. Lower SEP was associated with higher frailty prevalence across all indicators (childhood deprivation 7/8 studies, education 227/248, occupation 28/32, housing 8/9, income 98/108, wealth 39/44 and area-based deprivation 32/34). Lower SEP was also associated with higher frailty incidence (27/30), with greater odds of transitioning towards a more severe frailty state (35/43), lower odds of frailty reversion (7/11), and (in some studies) with more rapid accumulation of deficits (7/15). The relationship between frailty and mortality was not modified by SEP. INTERPRETATION: Preventative measures across multiple levels of individual and structural inequality are likely to be required to reduce the rising levels of frailty. Resourcing of interventions and services to support people living with frailty should be proportionate to needs in the population to avoid widening existing health inequalities.

A Multifunctional Nanocatalytic Metal-Organic Framework as a Ferroptosis Amplifier for Mild Hyperthermia Photothermal Therapy.

Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor self-protection, immunosuppression, metastasis, and recurrence. To address this issue, we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy (mild PTT) based on cisplatin (DDP) and a ferrocene metal-organic framework (MOF-Fc) nanocomposite, which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses. Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA. The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity, magnifying mild hyperthermia effects via the radical oxygen species (ROS)-adenosine triphosphate (ATP)-HSP silencing pathway, with important implications for clinical hyperthermia therapy.

Development and validation of gestational diabetes mellitus health literacy scale.

OBJECTIVE: While there are various health literacy scales that exist, none of health literacy scale suitable for pregnant women with gestational diabetes mellitus (GDM). To address this gap, this study aimed to develop GDM health literacy scale and evaluate its psychometric properties. METHODS: Based on the Delphi expert consultation, we developed the initial GDM health literacy scale. Item analysis was taken using a sample (n = 299) recruited in China to form formal scale. Additional participants (n = 395) completed survey to assess the internal consistency reliability, test-retest reliability, content validity, construct validity and criterion correlation validity of scale. RESULTS: The scale performed well in terms of internal consistency reliability, content validity, construct validity and criterion correlation validity. Test-retest reliability indicated that the instrument was effective at measuring health literacy of GDM over time. CONCLUSION: The scale is a reliable and valid measure of six domains of health literacy for GDM. PRACTICE IMPLICATIONS: The scale can be used to effectively evaluate the level of health literacy of pregnant women with GDM. The information can provide targeted health support for pregnant women with GDM to improve their health literacy and self-management ability.

Metagenomic Next-Generation Sequencing as an Effective Diagnostic Tool for Talaromycosis in HIV-Negative Patients.

The diagnosis of Talaromyces marneffei infection in HIV-negative patients remains challenging. There is an urgent need for rapid and convenient methods to diagnose this complicated disease. The aim of this study was to evaluate the diagnostic efficiency of metagenomic next-generation sequencing (mNGS) for talaromycosis in non-HIV-infected patients by comparing mNGS with traditional microbial culture. In total, 66 samples from 57 patients were analyzed via both mNGS and microbial culture. The ROC curve showed a sensitivity for mNGS of 97.22%, which was greater than that of microbial culture (61.11%). Samples from the respiratory tract, infectious skin lesions, and lymph nodes are recommended as routine samples for talaromycosis detection via mNGS. Furthermore, mNGS significantly reduced the diagnostic time compared to microbial culture. Overall, our study demonstrated that mNGS is a promising tool for rapid and accurate pathogenic detection in HIV-negative patients with talaromycosis.

SMARCA4­deficient uterine adnexal tumor with ascites: A case report and literature review.

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4)-deficient tumors are rare and highly aggressive tumors characterized by a loss of SMARCA4 expression, and SMARCA4-deficient tumors in the adnexal area of the uterus are particularly rare. The present study describes the case of a 64-year-old woman who was admitted to Weifang People's Hospital (Weifang, China) with abdominal distension, and was observed to have a mass with ascites in the adnexal area of the uterus. Based on clinical, imaging and pathological findings, the patient was diagnosed with a SMARCA4-deficient adnexal tumor with ascites. Biopsy of the left and right adnexal lesions was performed, and the patient was administered chemotherapy. After one cycle of bevacizumab, sindilizumab and carboplatin, no further treatment was administered. After biopsy and chemotherapy, the abdominal distension was alleviated and the general condition of the patient was satisfactory. The patient was followed up and died 3 months after treatment. Notably, it is important to avoid misdiagnosing this tumor as other types of adnexal uterine tumors, and morphological and immunohistochemical features may be useful for diagnosing primary SMARCA4-deficient tumors in the adnexal area of the uterus.

Endosome mediated nucleocytoplasmic trafficking and endomembrane allocation is crucial to polyglutamine toxicity.

Aggregation of aberrant proteins is a common pathological hallmark in neurodegeneration such as polyglutamine (polyQ) and other repeat-expansion diseases. Here through overexpression of ataxin3 C-terminal polyQ expansion in Drosophila gut enterocytes, we generated an intestinal obstruction model of spinocerebellar ataxia type3 (SCA3) and reported a new role of nuclear-associated endosomes (NAEs)-the delivery of polyQ to the nucleoplasm. In this model, accompanied by the prominently increased RAB5-positive NAEs are abundant nucleoplasmic reticulum enriched with polyQ, abnormal nuclear envelope invagination, significantly reduced endoplasmic reticulum, indicating dysfunctional nucleocytoplasmic trafficking and impaired endomembrane organization. Consistently, Rab5 but not Rab7 RNAi further decreased polyQ-related NAEs, inhibited endomembrane disorganization, and alleviated disease model. Interestingly, autophagic proteins were enriched in polyQ-related NAEs and played non-canonical autophagic roles as genetic manipulation of autophagic molecules exhibited differential impacts on NAEs and SCA3 toxicity. Namely, the down-regulation of Atg1 or Atg12 mitigated while Atg5 RNAi aggravated the disease phenotypes both in Drosophila intestines and compound eyes. Our findings, therefore, provide new mechanistic insights and underscore the fundamental roles of endosome-centered nucleocytoplasmic trafficking and homeostatic endomembrane allocation in the pathogenesis of polyQ diseases.

Innovative rapid liquid concentration measurement based on thermal lens effect and machine learning.

This study addresses the critical need for rapid and online measurement of liquid concentrations in industrial applications. Although the thermal lens effect (TLE) is extensively explored in laser systems for determining thermal lens focal lengths, its application in quantifying solution concentrations remains underexplored. This research explores the relationship between various liquid concentrations and the interference fringes induced by the TLE. A novel approach is introduced, utilizing TLE to measure solution concentrations, with integration of image processing and discrete Fourier transform (DFT) techniques for feature extraction from interference rings. Further, machine learning, specifically backpropagation artificial neural network (BP-ANN), is employed to model concentration measurement. The model demonstrates high accuracy, evidenced by low root mean square error (RMSE) values of 3.055 and 5.396 for the training and test sets, respectively. This enables precise, real-time determination of soy sauce concentration, offering significant implications for industrial testing, environmental monitoring, and other related fields.

Description of subgroup reporting in clinical trials of chronic diseases: a meta-epidemiological study.

INTRODUCTION: In trials, subgroup analyses are used to examine whether treatment effects differ by important patient characteristics. However, which subgroups are most commonly reported has not been comprehensively described. DESIGN AND SETTINGS: Using a set of trials identified from the US clinical trials register (ClinicalTrials.gov), we describe every reported subgroup for a range of conditions and drug classes. METHODS: We obtained trial characteristics from ClinicalTrials.gov via the Aggregate Analysis of ClinicalTrials.gov database. We subsequently obtained all corresponding PubMed-indexed papers and screened these for subgroup reporting. Tables and text for reported subgroups were extracted and standardised using Medical Subject Headings and WHO Anatomical Therapeutic Chemical codes. Via logistic and Poisson regression models we identified independent predictors of result reporting (any vs none) and subgroup reporting (any vs none and counts). We then summarised subgroup reporting by index condition and presented all subgroups for all trials via a web-based interactive heatmap (https://ihwph-hehta.shinyapps.io/subgroup_reporting_app/). RESULTS: Among 2235 eligible trials, 23% (524 trials) reported subgroups. Follow-up time (OR, 95%CI: 1.13, 1.04-1.24), enrolment (per 10-fold increment, 3.48, 2.25-5.47), trial starting year (1.07, 1.03-1.11) and specific index conditions (eg, hypercholesterolaemia, hypertension, taking asthma as the reference, OR ranged from 0.15 to 10.44), predicted reporting, sponsoring source and number of arms did not. Results were similar on modelling any result reporting (except number of arms, 1.42, 1.15-1.74) and the total number of subgroups. Age (51%), gender (45%), racial group (28%) were the most frequently reported subgroups. Characteristics related to the index condition (severity/duration/types etc) were frequently reported (eg, 69% of myocardial infarction trials reported on its severity/duration/types). However, reporting on comorbidity/frailty (five trials) and mental health (four trials) was rare. CONCLUSION: Other than age, sex, race ethnicity or geographic location and characteristics related to the index condition, information on variation in treatment effects is sparse. PROSPERO REGISTRATION NUMBER: CRD42018048202.

Correlation analysis between BRAFV600E mutation and ultrasonic and clinical features of papillary thyroid cancer.

Purpose: The study investigates the value of the BRAFV600E mutation in determining the aggressiveness of papillary thyroid cancer (PTC) and its correlation with ultrasound features. Methods: The study selected 176 patients with BRAFV600E mutation and 80 without the mutation who underwent surgery at Guangxi Medical University Cancer Hospital. Clinical and pathological data were collected, focusing on BRAFV600E mutations and associated ultrasonic features. Correlation analysis, as well as univariate and multivariate logistic regression analysis, were conducted to identify independent risk factors for BRAFV600E mutation. The results were verified using a nomogram model. Results: The analysis results indicate that the BRAFV600E mutation correlates with tumor size, nodule size, taller-than-wide shape, margin, and shape of papillary thyroid cancer. The receiver operating characteristic curve was used to analyze the diagnostic effect of these features on BRAFV600E mutation. The results showed that nodule size had the most significant area under the curve (AUC = 0.665). Univariate and multivariate logistic regression analyses revealed that taller-than-wide shape ≥1, ill-defined margin, irregular shape, nodule size (≤1.40 cm), TT4 (>98.67 nmol/L), and FT3 (<4.14 pmol/L) were independent risk factors for BRAFV600E mutation. While considering all these factors in the nomogram, the Concordance index (C-index) remained high at 0.764. This suggests that the model has a good predictive effect. Conclusion: Ultrasound features including nodule size, taller-than-wide shape ≥1, ill-defined margins, irregular shape, higher TT4 levels, and lower FT3 levels were associated with papillary thyroid cancer aggressiveness and BRAFV600E mutation.

VP2 mediates the release of the feline calicivirus RNA genome by puncturing the endosome membrane of infected cells.

Feline calicivirus (FCV) is one of the few members of the Caliciviridae family that grows well in cell lines and, therefore, serves as a surrogate to study the biology of other viruses in the family. Conley et al. (14) demonstrated that upon the receptor engagement to the capsid, FCV VP2 forms a portal-like assembly, which might provide a channel for RNA release. However, the process of calicivirus RNA release is not yet fully understood. Our findings suggest that the separation of the FCV capsid from its genome RNA (gRNA) occurs rapidly in the early endosomes of infected cells. Using a liposome model decorated with the FCV cell receptor fJAM-A, we demonstrate that FCV releases its gRNA into the liposomes by penetrating membranes under low pH conditions. Furthermore, we found that VP2, which is rich in hydrophobic residues at its N-terminus, functions as the pore-forming protein. When we substituted the VP2 N-terminal hydrophobic residues, the gRNA release efficacy of the FCV mutants decreased. In conclusion, our results suggest that in the acidic environment of early endosomes, FCV VP2 functions as the pore-forming protein to mediate gRNA release into the cytoplasm of infected cells. This provides insight into the mechanism of calicivirus genome release.IMPORTANCEResearch on the biology and pathogenicity of certain caliciviruses, such as Norovirus and Sapovirus, is hindered by the lack of easy-to-use cell culture system. Feline calicivirus (FCV), which grows effectively in cell lines, is used as a substitute. At present, there is limited understanding of the genome release mechanism in caliciviruses. Our findings suggest that FCV uses VP2 to pierce the endosome membrane for genome release and provide new insights into the calicivirus gRNA release mechanism.

Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

An Evidence Map of Clinical Practice Guideline Recommendations on Stroke Rehabilitation.

ABSTRACT: The purpose of this study was to provide an evidence map for explaining research trends and gaps. Four databases and CPGs-related websites were searched up to March 2022. Basic information, methodological quality, reporting quality of CPGs, and similar stroke recommendations were extracted. The methodological and reporting quality of stroke CPGs were evaluated using the AGREE II instrument and the RIGHT checklist. The bubble plot format of the evidence map helped visualize the overall quality. Data management and analysis were performed using Excel 2013 and SPSS 22.0 software. A total of 12 CPGs, published between 1997 and 2020 were included for in-depth analysis. The identified CPGs had a mixed quality and scored poorly in the developmental rigor and applicability domains by AGREE II. According to the RIGHT checklist, field four (clarity of expression) showed the highest (79.2%), and field three (rigor of formulation) secured the lowest (28%) reporting rates. The stroke rehabilitation recommendations primarily focused on organizational management, timing and intensity, rehabilitation and nutritional management of dysphagia, return to work, communication, speech, and language function. This would promote improvement in developing trustworthy CPGs for stroke rehabilitation.